Regulation of cytotoxic T lymphocyte-associated molecule-4 by Src kinases
- Authors
- Chuang E.; Lee K.-M.; Robbins M.D.; Duerr J.M.; Alegre M.-L.; Hambor J.E.; Neveu M.J.; Bluestone J.A.; Thompson C.B.
- Issue Date
- 1999
- Citation
- Journal of Immunology, v.162, no.3, pp 1270 - 1277
- Pages
- 8
- Indexed
- SCOPUS
- Journal Title
- Journal of Immunology
- Volume
- 162
- Number
- 3
- Start Page
- 1270
- End Page
- 1277
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/24319
- ISSN
- 0022-1767
1550-6606
- Abstract
- Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a cell surface receptor expressed to activated T cells that can inhibit T cell responses induced by activation of the TCR and CD28. Studies with phosphorylated peptides based on the CTLA-4 intracellular domain have suggested that tyrosine phosphorylation of CTLA-4 may regulate its interactions with cytoplasmic proteins that could determine its intracellular trafficking and/or signal transduction. However, the kinase(s) that phosphorylate CTLA-4 remain uncharacterized. In this report, we show that CTLA-4 can associate with the Src kinases Fyn and Lck and that transfection of Fyn or Lck, but not the unrelated kinase ZAP70, can induce tyrosine phosphorylation of CTLA-4 on residues Y201 and Y218. A similar pattern of tyrosine phosphorylation was found in pervanadate-treated Jurkat T cells stably expressing CTLA-4. Phosphorylation of CTLA-4 Y201 in Jurkat cells correlated with cell surface accumulation of CTLA-4. CTLA-4 phosphorylation induced the association of CTLA-4 with the tyrosine phosphatase SHP-2, but not with phosphatidylinositol 3-kinase. In contrast, Lck-induced phosphorylation of CD28 resulted in the recruitment of phosphatidylinositol 3-kinase, but not SHP-2. These findings suggest that phosphorylation of CD28 and CTLA-4 by Lck activates distinct intracellular signalling pathways. The association of CTLA-4 with Src kinases and with SHP-2 results in the formation of a CTLA-4 complex with the potential to regulate T cell activation.
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- Appears in
Collections - 1. Basic Science > Department of Biochemistry and Molecular Biology > 1. Journal Articles
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